Alzheimer’s disease (AD) is the most prevalent age related neurodegenerative disorder manifested by progressive cognitive decline and neuronal loss in the brain, yet precise etiopathology of majority of sporadic or late-onset AD cases is unknown. AD is associated with various pathological events such as Aβ deposition due to BACE-1 induced cleavage of APP, neuroinflammation, increased cholesterol synthesis, cholinergic deficit and oxidative stress. It was found that bone drug, alendronate (ALN) that cross blood brain barrier inhibits brain cholesterol synthesis and AChE enzyme activity. As cholesterol modifying agents have been supposed to alter AD like pathologies, the current study was designed to investigate the possible neuroprotective and therapeutic potential of ALN against ICV STZ induced experimental sporadic AD (SAD) in mice in a non-cholesterol dependent manner, using donepezil (5 mg/kg) as a reference standard. The preliminary study was done by molecular modelling to identify the binding affinity of ALN with BACE-1 in silico. The prevention of cognitive impairment in mice induced by ICV STZ (3 mg/kg) infused on first and third day, by ALN (1.76 mg/kg p.o.) administered for 15 consecutive days was assessed through Spontaneous Alternation Behavior (SAB) and Morris water maze (MWM) test. Additionally, the protective effect of ALN was also observed by the reversal of altered levels of Aβ_1-42, BACE-,1 neuroinflammatory cytokines, AChE activity and oxidative stress markers (except TBARS) in ICV-STZ infused mice. However, the findings of the present study imply the therapeutic potential of ALN against SAD-like complications.

阿尔茨海默病 (AD) 是最普遍的与年龄相关的神经退行性疾病，表现为进行性认知衰退和大脑神经元丢失，但大多数散发或迟发性 AD 病例的确切病因病理学尚不清楚。AD 与各种病理事件相关，例如由于 BACE-1 诱导的 APP 裂解导致的 Aβ 沉积、神经炎症、胆固醇合成增加、胆碱能缺陷和氧化应激。研究发现，穿过血脑屏障的骨药阿仑膦酸盐 (ALN) 会抑制脑胆固醇合成和 AChE 酶活性。由于胆固醇调节剂被认为可以改变类似 AD 的病症，目前的研究旨在以多奈哌齐 (5 mg/kg) 作为参考标准，以非胆固醇依赖性方式研究 ALN 对小鼠 ICV STZ 诱导的实验性散发性 AD (SAD) 的可能神经保护和治疗潜力。初步研究通过分子建模来确定 ALN 与 BACE-1 的结合亲和力在计算机中。通过自发交替行为 (SAB) 和莫里斯水评估了在第一天和第三天输注 ALN (1.76 mg/kg po) 连续 15 天输注 ICV STZ (3 mg/kg) 对小鼠认知障碍的预防作用迷宫 (MWM) 测试。此外，还通过逆转 ICV-STZ 输注小鼠中Aβ _1-42 、BACE-、1 神经炎性细胞因子、AChE 活性和氧化应激标志物（TBARS 除外）水平的改变观察到 ALN 的保护作用。然而，本研究的结果暗示了 ALN 对 SAD 样并发症的治疗潜力。